功能化核酸增强原发性肝癌荧光可视化成像研究

Primary liver cancer is ranked as the fifth most common malignant cancer and the second leading cause of cancer-related death in China. The early-stage diagnosis of this cancer remains unsatisfactory because of the limited success and false positive/negative results. To tackle these challenges, in this project, we propose to perform fluorescence visualization of the tumor by exploring the tumor specific protoporphyrin IX (PPIX). PPIX is metabolically produced after 5-aminolevulinic acid (5-ALA) administration and the fluorescence of PPIX is enhanced by guanine-rich DNA. To enhance the fluorescence of PPIX in vivo, the designed guanine-rich DNA should be delivered into tumor tissues by a nucleic acid delivery system (NDS). Thereafter the model mouse with primary liver cancer will be employed to evaluate the tumor targeting and imaging efficacy. Finally, the NDS will be optimized to satisfy the demand of clinical trials. It is expected that this project will provide beneficial guidance for early-stage diagnosis of primary liver cancer, which in turn will help to achieve the Major Research Plan of the National Natural Science Foundation of China entitled “Visualization of Functional Molecules for Tumor Progression and Diagnosis Studies”.

原发性肝癌在我国恶性肿瘤的发病率位列第五，其死亡率居第二位，但目前仍存在早期诊出率低、假阴性/假阳性高等缺点。针对此挑战，本项目以肿瘤组织摄取5-氨基乙酰丙酸（5-ALA）后特异性高表达荧光性原卟啉IX（PPIX）为基础，利用核酸传输体系将PPIX荧光增强性核酸递送到肿瘤区域，实现对肿瘤区域的PPIX进行荧光增强，从而提升肿瘤荧光可视化成像效果。通过理论分析与设计，联系实验研究和比较手段，研究核酸传输体系的结构和性质对其肿瘤靶向性能以及核酸递送效果的调控规律，在肝癌肿瘤动物模型中探究其在原发性肝癌中的荧光成像效果，以期建立高效可控的核酸递送体系，试图实现在临床上具有应用价值的肿瘤荧光探针的设计与制备，为原发性肝癌的可视化诊断构筑新的方法和平台。本项目预期所取得的研究成果将为原发性肝癌的早期检测和诊断提供有益的思路，能有力推动“肿瘤演进与诊疗的分子功能可视化研究重大研究计划”总体目标的实现。

肿瘤是严重危害民众生命健康的一大类疾病。肿瘤的发生与发展涉及一系列复杂的生物学过程，这给其诊疗带来了巨大挑战。构筑功能探针，用于肿瘤演进过程的研究则有助于人们理解肿瘤的生物学机制并将帮助人们建立新的诊疗手段。本项目基于功能化核酸与功能纳米材料，构建可用于肿瘤的成像与治疗的探针材料；通过调控免疫系统，并结合化疗、光热等实现肿瘤的有效治疗；利用探针材料的磁性、光声响应等性能，发展光声成像和核磁共振成像，以有助于肿瘤可视化研究等。相关研究成果对于创建肿瘤诊疗新模式和新技术具有一定的启发意义和推动作用。